A 27-year-old man with poorly controlled type 1 diabetes mellitus (average hemoglobin A1c of 15%) presented with a 1-week history of progressive pressure-like right upper abdominal discomfort associated with early satiety and nausea. On physical exam, he had firm hepatomegaly extending into the right pelvis. Laboratory testing revealed an aspartate aminotransferase = 6720 U/L (normal, 8–43 U/L), alanine aminotransferase level = 2549 U/L (normal, 7–45 U/L), alkaline phosphatase = 529 U/L (normal, 41–108 U/L), total bilirubin = 1.7 mg/dL (normal 0.1–1.0 mg/dL), with direct bilirubin = 1.5 mg/dL (normal 0.0–0.3 mg/dL) and a normal international normalized ratio. A computed tomography (CT) scan of the abdomen showed massive hepatomegaly of increased density as compared to the spleen (Fig. 1). Infectious and autoimmune causes of liver disease were excluded by laboratory testing. A liver biopsy was obtained and revealed preserved parenchymal architecture and enlarged pale hepatocytes (Fig. 2) with abundant cytoplasmic glycogen deposits demonstrated by periodic acid-Schiff stain (Fig. 3) and diastase digestion removing the glycogen resulting in “ghost cells” (Fig. 4). These histologic findings are characteristic of glycogenic hepatopathy.
The combination of a history of poorly controlled diabetes mellitus, acute liver injury indicated by marked elevation in aminotransferases, and the characteristic histologic changes on liver biopsy are diagnostic of glycogenic hepatopathy.1 It was first described as part of Mauriac's syndrome in 1930.2 This syndrome consists of glycogen loading, hepatomegaly, and abnormal liver enzymes in association with growth retardation and cushingoid features. It is recognized that glycogenic hepatopathy can present without the complete features of Mauriac syndrome,3 as in our patient. The liver biopsy typically shows numerous swollen and pale-staining hepatocytes on hematoxylin and eosin stains with excess glycogen accumulation demonstrated by periodic acid-Schiff stains. Additional histologic features include prominent glycogenated nuclei, giant mitochondria, and scattered acidophilic bodies. Liver test abnormalities vary significantly in glycogenic hepatopathy from normal to 10 times the upper limits of normal in some cases. The marked elevation in aminotransferases in our patient is much greater than described in the literature,1 raising the question of whether the clinical presentation is solely related to glycogenic hepatopathy. The other three main causes of liver enzyme elevations to this degree include: ischemic hepatopathy, herpetic hepatitis, and acetaminophen-induced liver injury. There were no clinical, laboratory, or histologic features to support these three entities as contributors to the marked liver test abnormalities. However, there are often no identifiable predisposing factors to ischemic hepatopathy, making it difficult to exclude concomitant ischemic insult to the liver in this case.
Glycogenic hepatopathy is seen in patients with poorly controlled insulin-dependent diabetes mellitus. The other main cause of liver enlargement and deranged liver tests related in diabetes mellitus is fatty liver. It is important to distinguish these two entities, because the pathobiology and therapy are different. Fatty liver is associated with hyperinsulinemia, mild elevation in liver enzymes, and a hypodense liver on CT, whereas glycogen loading of the liver typically occurs with insulin deficiency, may have a marked elevation in liver enzymes, and the liver is hyperdense on CT. The bright liver on CT scan without the administration of contrast can be a clue to the diagnosis of glycogenic hepatopathy. The other causes of a marked increase in hepatic attenuation (75 Hounsfield units) on an unenhanced CT are limited to conditions in which radiodense material is deposited in the liver such as iodine in patients using amiodarone and iron overload in hemochromatosis.4 Our patient had resolution of hepatomegaly on physical examination and normalization of liver enzymes after 3 months of optimized glycemic control.